The controlled and uncontrolled oxidation of lipid plays an extremely important role in the body. Uncontrolled oxidation of phospholipid in membranes has been suggested as the cause of the toxic lesion in a variety of pathological states. Controlled oxidation products derived from arachidonic acid via the prostaglandin pathway have been shown to be important factors in the chemistry of blood platelet aggregation. Prostacyclin (PGX), derived from PGH2, acts to inhibit the aggregation of blood platelets induced by prostaglandin endoperoxides. Thus, prostacyclin is thought to play an important role as a natural protective agent against heart attack and stroke. Lipid hydroperoxides have been shown to inhibit the formation of prostacyclin and thus these peroxides may play an important physiological role. Because of the potential importance of peroxides and prostacyclin in blood and membrane pathologies, we propose to study three aspects of the chemistry of these compounds: (1) Synthetic efforts are being directed toward the chemical synthesis of peroxides analogous to the known inhibitors of prostacyclin formation; (2) Related to these efforts, phospholipid hydroperoxides, the proposed first-formed product of membrane destruction, will also be prepared; and (3) Methods for the synthesis of thiaprostacyclin are being developed. Thiaprostacyclin should be a longer-lived analog of the parent molecule physiologically and thus may qualify as a more useful drug than the natural compound. The chemistry and pharmacology of all three classes of compounds, once prepared, will be thoroughly investigated.